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Cancer Medicine Sep 2023The main therapy for rectal cancer patients is neoadjuvant therapy (NT) followed by surgery. Immune biomarkers are emerging as potential predictors of the response to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The main therapy for rectal cancer patients is neoadjuvant therapy (NT) followed by surgery. Immune biomarkers are emerging as potential predictors of the response to NT. We performed a meta-analysis to estimate their predictive significance.
METHODS
A systematic literature search of PubMed, Ovid MEDLINE and EMBASE databases was performed to identify eligible studies. Studies on patients with rectal cancer undergoing NT in which the predictive significance of at least one of the immunological markers of interest was assessed by immunohistochemistry (IHC) in pretreatment biopsies were included.
RESULTS
Seventeen studies reporting sufficient data met the inclusion criteria for meta-analysis. High levels of total CD3+, CD4+ and CD8+ tumor infiltrating lymphocytes (TILs), as well as stromal and intraepithelial CD8+ compartments, significantly predicted good pathological response to NT. Moreover, high levels of total (tumoral and immune cell expression) PD-L1 resulted associated to a good pathological response. On the contrary, high levels of intraepithelial CD4+ TILs were correlated with poor pathological response. FoxP3+ TILs, tumoral PD-L1 and CTLA-4 were not correlated to the treatment response.
CONCLUSION
This meta-analysis indicated that high-density TILs might be predictive biomarkers of pathological response in patients that underwent NT for rectal cancer.
Topics: Humans; B7-H1 Antigen; Neoadjuvant Therapy; CD8-Positive T-Lymphocytes; Biomarkers; Rectal Neoplasms; Biopsy; Lymphocytes, Tumor-Infiltrating; Prognosis
PubMed: 37537787
DOI: 10.1002/cam4.6423 -
Journal of Diabetes Science and... Mar 2020Insulin infusion pump, continuous glucose monitoring (CGM), and insulin infusion set (IIS) have been developed to be increasingly feasible for people with type 1...
Insulin infusion pump, continuous glucose monitoring (CGM), and insulin infusion set (IIS) have been developed to be increasingly feasible for people with type 1 diabetes (T1D). Several recently approved CGMs are transitioning from 7-day to 10-day wear time without the need for fingerprick recalibration. Nevertheless, studies and improvements on IIS, a critical part of insulin pump therapy, have been limited. In particular, the recommended wear time of IIS is still 2-3 days, which can hardly match the current duration of CGM for potential closed-loop system development. It is generally believed that both the inserted catheter and the subsequent infused insulin drug could induce particular subcutaneous tissue response and skin-related complications at the infusion site. In certain cases, poor glycaemic control, increased risk of hypoglycemia, and serious cosmetic impact on people with diabetes were observed. Skin complication has also been attributed as an important factor resulting users to discontinue insulin pump therapy. This article provides the rare systematic review of IIS induced subcutaneous tissue responses and skin complications, including the impacts from the inserted catheters, the subcutaneous infused insulin, and the adhesive or tape used to immobilize the catheter. The FDA's recommendation for the frequency of IIS change was further discussed. Future studies on this topic are required to further understand the IIS-related problems, and future strategies could be developed accordingly to significantly reduce the incidence of these problems, extend the wear time, and increase the acceptance of insulin pump based therapy.
Topics: Blood Glucose; Blood Glucose Self-Monitoring; Catheters; Diabetes Mellitus, Type 1; Foreign-Body Reaction; Humans; Infusions, Subcutaneous; Injection Site Reaction; Insulin Infusion Systems; Subcutaneous Tissue
PubMed: 30931603
DOI: 10.1177/1932296819837972 -
Frontiers in Immunology 2023Richter syndrome (RS) represents the clonal evolution of chronic lymphocytic leukemia with histological transformation into a high-grade B cell lymphoma (diffuse large B... (Meta-Analysis)
Meta-Analysis
INTRODUCTION AND AIMS
Richter syndrome (RS) represents the clonal evolution of chronic lymphocytic leukemia with histological transformation into a high-grade B cell lymphoma (diffuse large B cell lymphoma - DLBCL) or Hodgkin lymphoma. Considering that RS is an uncommon condition with poor prognosis, few high-quality evidence is available. To overcome this unmet need, this meta-analysis aimed to pool efficacy of early clinical trials in Richter syndrome (DLBCL subtype).
METHODS
MEDLINE, Scopus and Web of Science were searched up to May of 2023 to identify clinical trials decoying efficacy. The pooled complete response, objective response and intension-to-treat failure rates were calculated by pharmacological categories (classical chemotherapy, immunochemotherapy, immunotherapy, Bruton-tyrosine kinase inhibitors, targeted approaches, cell-based therapies and combinatorial regimens) using the Der-Simonian and Laird random-effects model. The Freeman-Tukey double arcsine method was used to estimate variance and confidence intervals. Heterogeneity was assessed using the I method.
RESULTS
Overall, from 1242 studies identified, 30 were included, pooling data from 509 patients. The higher efficacy rates when, cell-based therapies were excluded, were achieved by immunochemotherapeutic regimens followed by combinatorial regimens, with complete response rates of 21.54% (IC95%14.93-28.87) and 23.77% (IC95% 8.70-42.19), respectively. Bispecific antibodies (alone or coupled with a chemotherapy debulking strategy) overtook Bruton tyrosine kinase inhibitors response rates. The latter, although achieving objective response rates above average, presented scarce complete response rates. Checkpoint inhibitors alone usually do not lead to complete responses, but their effectiveness may improve when combined with other agents, unveiling the importance of immune microenvironmental modulation.
CONCLUSION
This is the first meta-analysis of early clinical trials assessing the impact of different therapeutics in RS. By analyzing the pooled efficacy estimates, our work suggests the role of a tailor-made bridging therapy for young patients with RS eligible for allogeneic hematopoietic stem cell transplantation (alloSCT), formally the only curative strategy.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Hodgkin Disease; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Tyrosine Kinase Inhibitors; Clinical Trials as Topic
PubMed: 38077330
DOI: 10.3389/fimmu.2023.1295293 -
Cureus Jun 2023An artificial intelligence (AI) program called ChatGPT that generates text in response to typed commands has proven to be highly popular, as evidenced by the fact that... (Review)
Review
An artificial intelligence (AI) program called ChatGPT that generates text in response to typed commands has proven to be highly popular, as evidenced by the fact that OpenAI makes it available online. The goal of the present investigation was to investigate ChatGPT's potential applications as an outstanding instance of large language models (LLMs) in the fields of public dental health schooling, writing for academic use, research in public dental health, and clinical practice in public dental health based on the available data. Importantly, the goals of the current review included locating any drawbacks and issues that might be connected to using ChatGPT in the previously mentioned contexts in healthcare settings. Using search phrases including chatGPT, implications, artificial intelligence (AI), public health dentistry, public health, practice in public health dentistry, education in public health dentistry, academic writing in public health dentistry, etc., a thorough search was carried out on the Pubmed database, the Embase database, the Ovid database, the Global Health database, PsycINFO, and the Web of Science. The dates of publication were not restricted. Systematic searches were carried out for all publications according to inclusion and exclusion criteria between March 31, 2018, and March 31, 2023. Eighty-four papers were obtained through a literature search using search terms. Sixteen similar and duplicate papers were excluded and 68 distinct articles were initially selected. Thirty-three articles were excluded after reviewing abstracts and titles. Thirty-five papers were selected, for which full text was managed. Four extra papers were found manually from references. Thirty-nine articles with full texts were eligible for the study. Eighteen inadequate articles are excluded from the final 21 studies that were finally selected for systemic review. According to previously published studies, ChatGPT has demonstrated its effectiveness in helping scholars with the authoring of scientific research and dental studies. If the right structures are created, ChatGPT can offer suitable responses and more time to concentrate on the phase of experimentation for scientists. Risks include prejudice in the training data, undervaluing human skills, the possibility of fraud in science, as well as legal and reproducibility concerns. It was concluded that practice considering ChatGPT's potential significance, the research's uniqueness, and the premise-the activity of the human brain-remains. While there is no question about the superiority of incorporating ChatGPT into the practice of public health dentistry, it does not, in any way, take the place of a dentist since clinical practice involves more than just making diagnoses; it also involves relating to clinical findings and providing individualized patient care. Even though AI can be useful in a number of ways, a dentist must ultimately make the decision because dentistry is a field that involves several disciplines.
PubMed: 37456464
DOI: 10.7759/cureus.40367 -
Current Oncology (Toronto, Ont.) Sep 2023Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation.... (Review)
Review
Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation. Low-grade serous ovarian cancer (LGSOC) is a rare histologic subtype that lacks disease-specific evidence-based treatment regimens. However, LGSOC is relatively chemo-resistant and has a poor response to traditional treatments. Alternative treatments, including biologic therapies such as bevacizumab, have shown some activity in LGSOC. Thus, the objective of this systematic review is to determine the effect and safety of bevacizumab in the treatment of LGSOC. Following PRISMA guidelines, Medline ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase all from the OvidSP platform, ClinicalTrials.gov, International Clinical Trials Registry Platform, International Standard Randomised Controlled Trial Number Registry were searched from inception to February 2022. Articles describing bevacizumab use in patients with LGSOC were included. Article screening, data extraction, and critical appraisal of included studies were completed by two independent reviewers. The effect of bevacizumab on the overall response rate, progression-free survival, overall survival, and adverse effects were summarized. The literature search identified 3064 articles, 6 of which were included in this study. A total of 153 patients were analyzed; the majority had stage IIIC cancer (56.2%). The overall median response rate reported in the studies was 47.5%. Overall, bevacizumab is a promising treatment for LGSOC, with response rates higher than traditional treatment modalities such as conventional chemotherapy, and is often overlooked as a treatment tool. A prospective clinical trial evaluating the use of bevacizumab in LGSOC is necessary to provide greater evidence and support these findings.
Topics: Humans; Female; Bevacizumab; Prospective Studies; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Serous; Peritoneal Neoplasms; Ovarian Neoplasms
PubMed: 37754507
DOI: 10.3390/curroncol30090592 -
International Journal of Surgery... Jan 2024The application of neoadjuvant immune checkpoint inhibitors combined with chemotherapy (NICT) in treating locally advanced oesophageal squamous cell carcinoma (ESCC) is... (Meta-Analysis)
Meta-Analysis
Comparison of efficacy and safety between neoadjuvant chemotherapy and neoadjuvant immune checkpoint inhibitors combined with chemotherapy for locally advanced esophageal squamous cell carcinoma: a systematic review and meta-analysis.
BACKGROUND
The application of neoadjuvant immune checkpoint inhibitors combined with chemotherapy (NICT) in treating locally advanced oesophageal squamous cell carcinoma (ESCC) is a subject of considerable research interest. In light of this, we undertook a comprehensive meta-analysis aiming to compare the efficacy and safety of this novel approach with conventional neoadjuvant chemotherapy (NCT) in the management of ESCC.
METHODS
A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science to gather relevant literature on the efficacy and safety of NICT compared to conventional NCT in locally advanced ESCC published before June 2023. Effect indicators, including odds ratios (ORs) with associated 95% CIs, were employed to evaluate the safety and efficacy outcomes. The risk of bias was assessed using the Cochrane bias risk assessment tool, and s ubgroup analysis and sensitivity analysis were conducted to investigate the findings further.
RESULTS
A total of nine studies qualified for the meta-analysis, all of which investigated the efficacy and safety of NICT compared to conventional NCT. The pooled rates of pathologic complete response and major pathologic response in the NICT group were significantly higher compared to the NCT group, with values of 26.9% versus 8.3% ( P <0.00001) and 48.1% versus 24.6% ( P <0.00001), respectively. The ORs for achieving pathologic complete response and major pathologic response were 4.24 (95% CI, 2.84-6.32, I 2 =14%) and 3.30 (95% CI, 2.31-4.71, I 2 =0%), respectively, indicating a significant advantage for the NICT group. Regarding safety outcomes, the pooled incidences of treatment-related adverse events and serious adverse events in the NICT group were 64.4% and 11.5%, respectively, compared to 73.8% and 9.3% in the NCT group. However, there were no significant differences observed between the two groups in terms of treatment-related adverse events (OR=0.67, 95% CI, 0.29-1.54, P =0.35, I 2 =58%) or serious adverse events (OR=1.28, 95% CI, 0.69-2.36, P =0.43, I 2 =0%). Furthermore, no significant differences were found between the NICT and NCT groups regarding R0 resection rates, anastomotic leakage, pulmonary infection, and postoperative hoarseness.
CONCLUSIONS
Neoadjuvant immune checkpoint inhibitors combined with chemotherapy demonstrate efficacy and safety in treating resectable oesophageal squamous cell carcinoma. Nevertheless, additional randomized trials are required to confirm the optimal treatment regimen.
Topics: Humans; Neoadjuvant Therapy; Esophageal Squamous Cell Carcinoma; Immune Checkpoint Inhibitors; Esophageal Neoplasms; Anastomotic Leak; Pathologic Complete Response
PubMed: 37800587
DOI: 10.1097/JS9.0000000000000816 -
International Journal of Surgery... Sep 2023Overall survival is the gold-standard outcome measure for phase 3 trials, but the need for a long follow-up period can delay the translation of potentially effective... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Overall survival is the gold-standard outcome measure for phase 3 trials, but the need for a long follow-up period can delay the translation of potentially effective treatment to clinical practice. The validity of major pathological response (MPR) as a surrogate of survival for non small cell lung cancer (NSCLC) after neoadjuvant immunotherapy remains unclear.
METHODS
Eligibility was resectable stage I-III NSCLC and delivery of PD-1/PD-L1/CTLA-4 inhibitors prior to resection; other forms/modalities of neoadjuvant and/or adjuvant therapies were allowed. Statistics utilized the Mantel-Haenszel fixed-effect or random-effect model depending on the heterogeneity ( I2 ).
RESULTS
Fifty-three trials (seven randomized, 29 prospective nonrandomized, 17 retrospective) were identified. The pooled rate of MPR was 53.8%. Compared to neoadjuvant chemotherapy, neoadjuvant chemo-immunotherapy achieved higher MPR (OR 6.19, 4.39-8.74, P <0.00001). MPR was associated with improved disease-free survival/progression-free survival/event-free survival (HR 0.28, 0.10-0.79, P =0.02) and overall survival (HR 0.80, 0.72-0.88, P <0.0001). Patients with stage III (vs I/II) and PD-L1 ≥1% (vs <1%) more likely achieved MPR (OR 1.66,1.02-2.70, P =0.04; OR 2.21,1.28-3.82, P =0.004).
CONCLUSIONS
The findings of this meta-analysis suggest that neoadjuvant chemo-immunotherapy achieved higher MPR in NSCLC patients, and increased MPR might be associated with survival benefits treated with neoadjuvant immunotherapy. It appears that the MPR may serve as a surrogate endpoint of survival to evaluate neoadjuvant immunotherapy.
Topics: Humans; Neoadjuvant Therapy; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Prospective Studies; Retrospective Studies; Lung Neoplasms; Prognosis; Immunotherapy
PubMed: 37247009
DOI: 10.1097/JS9.0000000000000496 -
Frontiers in Oncology 2022To evaluate the clinical curative effects and toxicity of neoadjuvant chemoradiotherapy for resectable gastric cancer compared to those of neoadjuvant chemotherapy.
OBJECTIVES
To evaluate the clinical curative effects and toxicity of neoadjuvant chemoradiotherapy for resectable gastric cancer compared to those of neoadjuvant chemotherapy.
METHODS
A systematic review and meta-analysis of the randomized controlled trials (RCTs) of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy were performed in patients with resectable gastric cancer.
RESULTS
Seven RCTs were included (601 patients; 302 in the neoadjuvant chemoradiotherapy group and 299 in the neoadjuvant chemotherapy group). The neoadjuvant chemoradiotherapy group had an increased number of patients with a complete response [odds ratio (OR) = 3.79, 95% confidence interval (CI): 1.68-8.54, p = 0.001] and improved objective response rate (OR = 2.78, 95% CI: 1.69-4.57, p < 0.0001), 1-year (OR = 3.51, 95% CI: 1.40-8.81, p = 0.007) and 3-year (OR = 2.14, 95% CI: 1.30-3.50, p = 0.003) survival rates, R0 resection rate (OR = 2.21, 95% CI: 1.39-3.50, p = 0.0008), and complete pathologic response (OR = 4.39, 95% CI: 1.59-12.14, p = 0.004). Regarding the incidence of adverse effects after neoadjuvant therapy, only the occurrence rate of gastrointestinal reaction in the neoadjuvant chemoradiotherapy group was higher than that in the neoadjuvant chemotherapy group (OR = 1.76, 95% CI: 1.09-2.85, p = 0.02), and there was no significant difference in other adverse effects. There was no difference in the incidence of postoperative complications between the two groups.
CONCLUSION
Neoadjuvant chemoradiotherapy for resectable gastric cancer has several advantages in terms of efficacy and safety compared to neoadjuvant chemotherapy. Therefore, neoadjuvant chemoradiotherapy has great potential as an effective therapy for resectable gastric cancers.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/inplasy-2022-3-0164, registration number INPLASY202230164.
PubMed: 35992846
DOI: 10.3389/fonc.2022.927119 -
Cancer Medicine May 2023Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) require multi-modality treatment. Immune checkpoint inhibitors (ICIs) are now standard of... (Review)
Review
BACKGROUND
Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) require multi-modality treatment. Immune checkpoint inhibitors (ICIs) are now standard of care in management of recurrent/metastatic HNSCC. However, its role in the definitive and neoadjuvant setting remains unclear.
METHODS
A literature search was conducted that included all articles investigating ICI in untreated locally advanced (LA) HNSCC. Data was extracted and summarised and rated for quality using the Cochrane risk of bias tool.
RESULTS
Of 1086 records, 29 met the final inclusion criteria. In both concurrent and neoadjuvant settings, the addition of ICI was safe and did not delay surgery or reduce chemoradiotherapy completion. In the concurrent setting, although ICI use demonstrates objective responses in all published trials, there has not yet been published data to with PFS or OS benefit. In the neoadjuvant setting, combination ICI resulted in superior major pathological response rates compared to ICI monotherapy without a significant increase adverse event profiles, but its value in improving survival is not clear. ICI efficacy appears to be affected by tumour characteristics, in particular PD-L1 combined positive score, HPV status and the tumour microenvironment.
CONCLUSIONS
There is significant heterogeneity of ICI use in untreated LA HNSCC with multiple definitive concurrent and neoadjuvant protocols used. Resultantly, conclusions regarding the survival benefits of adding ICI to standard-of-care regimens cannot be made. Further trials and translational studies are required to elucidate optimal ICI sequencing in the definitive setting as well as better define populations more suited for neoadjuvant protocols.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Head and Neck Neoplasms; Immunotherapy; Tumor Microenvironment
PubMed: 36934434
DOI: 10.1002/cam4.5815 -
Frontiers in Immunology 2024Neoadjuvant immunotherapy has demonstrated beneficial outcomes in various cancer types; however, standardized protocols for neoadjuvant immunotherapy in hepatocellular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neoadjuvant immunotherapy has demonstrated beneficial outcomes in various cancer types; however, standardized protocols for neoadjuvant immunotherapy in hepatocellular carcinoma (HCC) are currently lacking. This systematic review and meta-analysis aims to investigate the reliability of neoadjuvant immunotherapy's efficacy and safety in the context of HCC.
METHODS
A systematic search was conducted across PubMed (MEDLINE), EMBASE, the Web of Science, the Cochrane Library, and conference proceedings to identify clinical trials involving resectable HCC and neoadjuvant immunotherapy. Single-arm meta-analyses were employed to compute odds ratios and 95% confidence intervals (CIs). Heterogeneity analysis, data quality assessment, and subgroup analyses based on the type of immunotherapy drugs and combination therapies were performed. This meta-analysis is registered in PROSPERO (identifier CRD42023474276).
RESULTS
This meta-analysis included 255 patients from 11 studies. Among resectable HCC patients, neoadjuvant immunotherapy exhibited an overall major pathological response (MPR) rate of 0.47 (95% CI 0.31-0.70) and a pathological complete response (pCR) rate of 0.22 (95% CI 0.14-0.36). The overall objective response rate (ORR) was 0.37 (95% CI 0.20-0.69), with a grade 3-4 treatment-related adverse event (TRAE) incidence rate of 0.35 (95% CI 0.24-0.51). Furthermore, the combined surgical resection rate was 3.08 (95% CI 1.66-5.72). Subgroup analysis shows no significant differences in the efficacy and safety of different single-agent immunotherapies; the efficacy of dual ICIs (Immune Checkpoint Inhibitors) combination therapy is superior to targeted combined immunotherapy and monotherapy, while the reverse is observed in terms of safety.
DISCUSSION
Neoadjuvant immunotherapy presents beneficial outcomes in the treatment of resectable HCC. However, large-scale, high-quality experiments are warranted in the future to provide robust data support.
Topics: Humans; Carcinoma, Hepatocellular; Immune Checkpoint Inhibitors; Liver Neoplasms; Neoadjuvant Therapy; Reproducibility of Results
PubMed: 38440727
DOI: 10.3389/fimmu.2024.1352873